1. Field of the Invention
This invention is generally directed to pharmaceutical formulations with improved physical and chemical characteristics, comprising gabapentin in tablet form for oral administration. The tablet form can be prepared by spray-coating gabapentin with a binder solution and compressing the spray-coated gabapentin into non-friable, stable tablets. This invention is also generally directed to a method of producing pharmaceutical formulations in tablet form which contain large doses of active drug by spray-coating the active drug with a binder solution and compressing the spray-coated active drug into tablets.
2. Description of the Related Art
Prior art methods for improving the compression characteristics of pharmaceutical formulations involve introducing additional excipients, such as microcrystalline cellulose, as compression aids to prevent fracturing of granules and tablets. However, the inclusion of additional excipients can be expensive and time consuming, can effect the stability of the active drug agent, and can increase the size of the tablet.
Other methods for improving the compression characteristics of pharmaceutical formulations include dissolving the active drug in a binder solution to form a drug solution, spray drying the drug solution to form a powder and then compressing the powder into a tablet. This method, however, is inefficient because it requires a large amount of binder solution. Moreover, dissolving the active drug in a solution can cause stability problems, polymorph conversion, and changes in the crystalline structure of the drug.
U.S. Pat. No. 4,874,614 issued to Becker, discloses a method of preventing the fracture of coated drug granules during the compression process by incorporating into a matrix, along with the granules, microcrystalline cellulose in the amount from 10% to 50% by weight of the total matrix.
U.S. Pat. No. 5,725,884, issued to Sherwood et al., discloses the use of a microcrystalline cellulose based excipient comprising microcrystalline cellulose and silicon dioxide to improve the compressibility of the excipient microcrystalline cellulose, not the active drug substance.
U.S. Pat. No. 5,534,551, U.S. Pat. No. 4,533,674, U.S. Pat. No. 4,605,666 and U.S. Pat. No. 4,710,519 all disclose a method of producing a compressible tablet by dissolving the active agent in a solvent and a binder then spray drying the solution to obtain a spray dried powder that is suitable for direct compression.
IE 3089/90 to issued Augart, et. al., discloses a process for stabilizing pharmaceutical compositions containing gabapentin in solid form. The process entails hydrolyzing gabapentin with a semi-concentrated mineral acid and then converting gabapentin into a solid pharmaceutical composition containing hydroxypropyl methylcellulose, polyvinylpyrrolidine, crospovidone, maize starch, cyclodextrin, talcum, co-polymer of dimethylaminomethacrylic acid and/or neutral methacrylic acid ester.
Various patent applications and patents disclosing processes for preparing the gabapentin, and its methods of use are disclosed in PCT 98/28255, U.S. Pat. No. 4,024,175, U.S. Pat. No. 4,087,544, U.S. Pat. No. 5,084,479, U.S. Pat. No. 4,960,931, and U.S. Pat. No. 4,894,476.
It has been discovered that pharmaceutical formulations containing the active drug gabapentin can be produced with large doses of gabapentin but still be small enough for a patient to swallow. It has also been discovered that pharmaceutical formulations containing gabapentin in tablet form can be produced having improved characteristics such as hardness, friability and stability. It has further been discovered that the pharmaceutical formulations containing gabapentin can be produced in tablet form by spray-coating gabapentin particles with a binder solution and compressing the spray-coated particles into tablets. This method is also applicable to other pharmaceutical tablet formulations that require large doses of active drug for oral administration.
Thus, one aspect of the present invention is a pharmaceutical tablet comprising more than about 76% by weight of gabapentin. A second aspect of the invention is a pharmaceutical tablet comprising more than about 76% by weight of gabapentin, a friability of less than about 1%, a hardness of about 10 kp to about 20 kp and a lactam level, a major degradation product of gabapentin, of less than about 0.4% by weight of the tablet composition.
A first preferred embodiment of the invention is that the pharmaceutical tablet comprises more than about 88% by weight of gabapentin. A second preferred embodiment is that the tablet has a friability of less than about 0.8%. A third preferred embodiment is that the tablet has a hardness of about 14 kp to about 16 kp. A fourth preferred embodiment of the invention is that the tablet has a lactam level of less than 0.2%.
An additional aspect of the invention is a pharmaceutical tablet comprising more than about 76% by weight of gabapentin, said tablet being formed from gabapentin particles spray-coated with a binder solution, mixed with a disintegrant and a lubricant, and then compressed into the tablet.
Another aspect of the invention is a method of producing a pharmaceutical tablet comprising:
dissolving binder in a solvent to produce a binder solution;
spray-coating the binder solution on gabapentin particles to achieve spray-coated gabapentin particles; and
compressing the spray-coated gabapentin particles into a tablet for oral administration to a patient,
where the tablet contains more than 76% by weight of gabapentin.
A further aspect of this invention is a method of producing a pharmaceutical tablet comprising:
dissolving binder in a solvent to produce a binder solution;
spray-coating the binder solution on active drug particles to achieve spray-coated active drug particles; and
compressing the spray-coated active drug particles into a tablet for oral administration to a patient,
where the tablet contains about 500 mg to about 1200 mg of active drug.
With the foregoing and other objects, advantages and features of the invention that will become herein after apparent, the nature of the invention may be more clearly understood by reference to the following detailed description and to the appended claims.